Guidelines for Managing Medical Emergencies
Blistering Skin disorders
Authors: Dr Murtaza Khan (SpR) and Dr J Gach (Consultant Dermatologist)
Email joanna.gach@uhcw.nhs.uk
Blistering skin conditions can be classified according to their aetiology as:
Insect bites
Infections e.g. shingles
Immune mediated e.g. bullous pemphigoid
Drug induced e.g. barbiturates, diuretics
Congenital e.g. epidermolysis bullosa
Metabolic e.g. porphyria cutanea tarda, diabetes
A blister is a localised swelling of the skin that contains clear fluid. The term ‘vesicle’ is used to describe a
blister smaller than 5mm and ‘bulla’ implies a blister larger than 5mm.
Vesicles Bullae
Insect bites
Clinical features:
Insect bite and sting reactions can manifest in a variety of skin lesions such as localized stinging, itching
and erythema, urticaria or even anaphylaxis. Occasionally the skin may react by forming blisters. It is
important to obtain a travel history from the patient and ask about pets or contact with animals.
Etiology:
The skin lesions develop as a result of an allergic reaction to the insect’s secretions.
Diagnosis:
This is made on the basis of history and examination.
Treatment:
Tense blisters should be punctured with a sterile needle and the roof should be left intact. Oral
antihistamines, calamine lotion and topical steroids may provide symptomatic relief.
Bullous flea bites
Infective blistering diseases
Blisters can result from bacterial or viral infections.
(i) Bacterial :
The two important bacterial disorders that result in blisters are staphylococcal scalded skin syndrome and
bullous impetigo
a. Staphylococcal scalded skin syndrome (SSSS)
Clinical features :
SSSS is seen in children less than 5 years of age. There is a prodrome of fever, malaise and
irritability followed by painful erythema, widespread bullae or erosions and perioral crusting.
Etiology:
This disease results from haematogenous spread of exfoliative toxins produced by certain strains
of staphylococcus aureus. The original infection may affect the mouth, nose, throat or umbilicus.
Diagnosis:
The diagnosis is mainly based on the clinical features. Blood inflammatory markers are raised and
blood cultures or cultures from the primary source of infection may reveal staphylococci. A skin
biopsy can help with diagnosis if there is clinical uncertainty.
Management:
Patients with SSSS require hospitalization for intravenous antibiotics, pain relief, skin care and
maintenance of fluids and electrolytes.
Staphylococcal scalded skin syndrome
b. Bullous impetigo
Clinical features :
This is most commonly seen in infants and often affects the diaper area. Patients develop flaccid
bullae with some surrounding erythema but are usually not systemically unwell.
Etiology:
Like SSSS this disease is also caused by exfoliative staphylococcal toxins but these are released
locally rather than spreading via the bloodstream.
Diagnosis:
Clinical features and isolation of staphylococcus from skin lesions are diagnostic.
Management:
Hospitalization is usually not necessary. Local or oral antibiotics are effective and the lesions heal
without scarring.
Bullous impetigo
c. Bullous cellulitis
Clinical features
Large blisters are seen on a background of cellulitis characterised by erythema, increased
warmth, oedema and tenderness. The patient may be febrile and generally unwell with malaise
and loss of appetite.
Etiology
Bullae form as a result of staphylococcal exfoliative toxins.
Diagnosis
This is based on the clinical features described above. Blood tests show raised markers of
inflammation. Blood cultures may confirm bacterial infection.
Management
Patients with bullous cellulitis require anti staphylococcal antibiotics, analgesia and limb
elevation. Blisters should be burst with a sterile needle and the roof should be left intact.
(ii) Viral :
Blistering diseases caused by viruses include cold sores, eczema herpeticum, chicken pox and shingles.
a. Cold sores
Clinical features :
Cold sores are characterised by grouped vesicles on the face and mouth. They usually appear
when patients have fever and can be recurrent. Periocular lesions and eye involvement can also
occur. Erythema multiforme is a possible complication.
Etiology:
They are caused by Herpes simplex virus (HSV) type 1.
Diagnosis :
The diagnosis is usually clinical but HSV DNA can be detected by PCR.
Management:
They usually heal on their own but topical acyclovir can be applied for quicker relief. Sometimes
oral acyclovir is used to prevent recurrent lesions and erythema multiforme.
Cold sores
b. Eczema herpeticum
Clinical features:
This disease presents in all ages but is more common in children. Patients usually have a history of
atopic eczema or other chronic skin condition. Clusters of fluid or pus filled vesicles are seen on an
erythematous base. Patients may be febrile and unwell. Skin lesions can develop secondary
bacterial infection.
Etiology:
Eczema herpeticum is caused by infection with Herpes simplex virus type 1 or 2.
Diagnosis:
The history, clinical features and skin swab for detection of viral DNA by PCR are diagnostic. Swabs
for bacterial culture should also be obtained.
Management:
Hospitalization may be required and patients are given oral or intravenous acyclovir. Secondary
bacterial infection is treated with system antibiotics. A regular cleansing moisturiser should be
used and steroid preparations should be avoided. If the eyes or eyelids are involved an
ophthalmologist should be consulted immediately.
Eczema herpeticum
c. Chicken pox
Clinical features:
Chicken pox or varicella may affect any age but is commonly seen in children. It presents as
multiple and widespread vesicles in different stages of development. Children are usually
systemically well but the disease in adults is accompanied by fever, headache, and malaise and
may lead to life threatening complications such as pneumonia or encephalitis.
Etiology:
Varicella results from primary infection with Herpes zoster virus (HZV). It is highly contagious and
the route of transmissions is either airborne or direct contact with infected fluid.
Diagnosis:
The clinical appearance of the rash is usually diagnostic. It is useful to obtain a history of contact
with affected individuals.
Management:
This is mainly symptomatic. Calamine lotion, antihistamines and paracetamol can be used to ease
discomfort and itching. Adults are usually given oral acyclovir to prevent complications.
Chicken pox with vesicles in various stages of development
d. Shingles
Clinical features:
Shingles or herpes zoster presents as a painful vesicular eruption in a single dermatome in adults
and elderly patients. There may be accompanying fever and lymphadenopathy.
Etiology:
The causative agent is herpes zoster virus (HZV) which is the same as varicella zoster virus that
causes chicken pox. The virus remains dormant in the anterior horn cells of the spinal cord until
the manifestation of shingles. Poor nutrition and decreased immunity e.g. diabetes can be
contributing factors.
Diagnosis :
The diagnosis is usually established on the basis of clinical features.
Management:
Acyclovir used early in the course of the illness can reduce the duration and severity of symptoms.
A vaccine is available for prevention in the elderly. Patients require regular pain killers such as
paracetamol but can be given agents specific for nerve pain such as amitriptyline or gabapentin.
Shingles affecting a single dermatome
Immune mediated blistering diseases
There important immune mediated blistering disorders are as follows:
(i) Bullous pemphigoid
(ii) Pemphigus vulgaris
(iii) Dermatitis Herpetiformis
(iv) Linear IgA disease
(i) Bullous pemphigoid :
Clinical features:
This disorder affects middle aged and elderly patients. Patients may have a long prodrome of itchy
skin before they develop the characteristic large and tense itchy bullae. They may develop blisters or
erosions inside the mouth.
Etiology:
It is an autoimmune disease caused by circulating antibodies targeted against the basement
membrane zone.
Diagnosis:
Skin auto antibodies can be detected in the serum. A skin biopsy shows a split between the epidermis
and dermis. Direct immunofluorescence of the skin sample shows deposition of immunoglobulin and
complement.
Management:
Patients are treated with oral steroids i.e. prednisolone with a slow and gradual reduction in the dose.
Immunosuppressant drugs such as Azathioprine can be used as steroid sparing agents.
Tense blisters in bullous pemphigoid
(ii) Pemphigus vulgaris:
Clinical features :
This immunobullous disease can affect young and elderly patients equally. It is a more serious clinical
entity than bullous pemphigoid and is characterised by flaccid bullae or erosions which are usually
widespread. The Nikolsky sign is positive and is exhibited by sliding of the epidermis on application of
firm pressure. Mucosal involvement is common with oral ulceration and conjunctivitis.
Etiology:
Pemphigus is an auto immune disease that results from antibodies against cell adhesion molecules
called desmosomes.
Diagnosis:
Like bullous pemphigoid circulating skin auto antibodies can be detected in pemphigus. A skin biopsy
is essential and shows separation of cells within the epidermis. Direct immunofluorescence of the
skin sample shows deposition of immunoglobulin and complement.
Management:
Patients with a large number of blisters and erosions may require hospitalization for dressings and
wound care. Oral lesions are treated with antiseptics, anti-inflammatory mouth washes and steroid
rinses. High doses of systemic steroids are usually required to suppress the disease and
immunosuppressants such as azathioprine, cyclophosphamide or mycophenolate are added.
Flaccid blisters and erosions in pemphigus vulgaris Oral involvement in pemphigus vulgaris
(iii) Dermatitis Herpetiformis:
Clinical features:
It is commonly seen in young adults who develop itchy vesicles on the scalp, face, elbows, buttocks or
knees. Patients may have clinical features or a family history of coeliac disease.
Etiology:
This autoimmune condition results from circulating antibodies against gluten.
Diagnosis:
This disease can be confirmed by blood tests which show the presence of Tissue Transglutaminase
(TTG) antibodies. A skin biopsy is performed to demonstrates blistering and deposition of IgA on
immunofluorescence.
Management:
Strict adherence to a gluten free diet is essential and can reduce the severity of the skin rash. Potent
topical steroids may be used and oral dapsone is the treatment of choice.
Typical distribution of vesicles in dermatitis herpetiformis
(iv) Linear IgA disease :
Clinical features:
Patients may experience itching long before the onset of skin lesions. In children bullae are usually
seen in the ano-genital area and on the face. In adults blisters are seen on the trunk and limbs.
Characteristically bullae are arranged in a ring pattern and this is termed the ‘cluster of jewels’ sign.
Oral ulceration or blisters and ocular discomfort are observed in some patients.
Etiology:
It is an immune mediated skin disease which is usually idiopathic but can be related to infections or
drugs such as vancomycin.
Diagnosis:
A skin biopsy is essential and shows blistering below the epidermis. Direct immunofluorescence
shows deposition of Immunoglobulin A in a linear pattern.
Management:
The disorder is usually treated with dapsone but oral steroids and other immunosuppressive drugs
are sometimes used instead.
Linear IgA disease with vesicles in a ring pattern
Drug induced blistering diseases
There are several distinct clinical forms of blistering drug eruptions:
(i) Fixed drug eruption :
A fixed drug eruption usually occurs in the same site each time the same drug is taken. The skin lesions
are characterised by well demarcated erythematous patches that develop oedema and often blisters.
They may be asymptomatic but sometimes cause itching or pain. These develop within a few hours of
exposure to the drug. They are commonly seen on the face, lips, arms, legs and genitalia. Drugs
commonly responsible for such reactions include paracetamol, aspirin, non-steroid anti-inflammatories
(NSAIDs), sulphonamides, tetracyclines and quinine. Treatment is usually not necessary but
antihistamines and topical steroids can be used for symptomatic relief.
Fixed drug eruption
(ii) Stevens-Johnson’s syndrome and Toxic epidermal necrolysis:
Stevens-Johsons’ syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious drug reactions that
affect the skin and mucosa. Both are considered to be part of the spectrum of the same disease process.
The skin lesions include erythematous macules and papules, targetoid lesions of erythema multiforme,
erosions and blisters. Erosions and ulcers may develop in the mouth, eyes and genitalia.
If less than 10% of the skin surface is involved the condition is termed SJS and if more than 35% of skin
surface is involved it is termed TEN. Between 10 and 35% involvement is termed SJS/TEN overlap
syndrome.
There are number of causative drugs e.g antibiotics including penicillin, cephalosporin and
sulphonamides, antifungal agents, antivirals, NSAIDs, anticonvulsants, etc. Management involves
cessation of the drug, admission to intensive care or burns unit, nutritional support, vigorous skin and
mucosal care and treatment of infection.
Erosions and blisters on the lips and erythema multiforme seen in SJS and TEN
(iii) Drug induced immunobullous disease:
Bullous pemphigoid, pemphigus vulgaris and linear IgA disease can develop as a result of systemic drugs.
The clinical and pathological characteristics are indistinguishable from the non-drug induced disease
described above. Numerous drugs such as antibiotics, analgesics, antihypertensives and anti-
inflammatories may be responsible. The skin disease usually resolves after stopping the drug.
(iv) Pseudoporphyria:
Drug induced pseudoporphyria is characterised by photosensitivity, skin fragility, vesicles and changes on
skin biopsy that are indistinguishable from porphyria. However porphyrin levels in the blood, faeces and
urine are normal. The causative drugs include NSAIDs, antibiotics, diuretics and retinoids. The treatment
involves stopping the drug and using sunscreens.
Congenital blistering diseases
The most important congenital cause of blistering is a group of disorders collectively termed
Epidermolysis Bullosa (EB).
Clinical features :
Children with EB usually develop blisters in the neonatal period or early childhood. Some forms may
present later in adolescence. Blisters form easily at sites of friction or minor trauma and there may be
associated abnormalities of the nails, teeth, respiratory tract and gastrointestinal system. Early
complications may arise such as skin infection, sepsis, malnutrition, and anemia and later in life skin
cancer.
Etiology:
These disorders result from genetic mutations that affect the anchoring complexes of the basement
membrane zone that lies between the epidermis and dermis. The pattern of inheritance may be
autosomal dominant or recessive.
Diagnosis:
The diagnosis is made on the basis of clinical features, skin biopsy with electron microscopy of the sample
and genetic tests for specific mutations. Antenatal diagnosis by chorionic villous sampling is also available.
Management:
There is no cure for EB and the management is centred on avoidance of trauma, gentle handling, aseptic
wound care and nutritional support. Genetic counselling is important for parents with an affected child.
Epidermolysis bullosa
Metabolic blistering diseases
Blisters can arise in patients with porphyria cutanea tarda (PCT) or diabetes.
(i) Porphyria cutanea tarda (PCT) :
Clinical features:
PCT is characterised by painful blistering on sun exposed areas and increased skin fragility. As the blisters
heal tiny cysts called milia may form. Patients can develop hepatitis and iron overload as complications.
Etiology:
This metabolic disease results from the accumulation of precursors of haem called porphyrins. This is
caused by a genetic deficiency of the enzyme uroporphyrinogen decarboxylase.
Diagnosis:
Detection of elevated levels of porphyrins in the urine and faeces establishes the diagnosis. A skin biopsy
can help to distinguish PCT from other bullous diseases. Serum iron stores and liver enzymes should be
monitored.
Management:
Patients are advised to avoid sunlight, wear protective clothing and apply sun blocks. Alcohol and drugs
that may trigger attacks such as hormonal contraceptives should be stopped. Reduction in iron stores by
repeated venesection can prevent attacks and complications from iron overload.
Blisters on hand in porphyria cutanea tarda
(ii) Bullous disease of diabetes:
Clinical features:
It presents with spontaneous bullae on the arms and legs. These are usually asymptomatic. There is
usually a longstanding history of diabetes.
Etiology:
Diabetes mellitus.
Diagnosis:
This is usually made on clinical features alone.
Management:
Diabetic bullae tend to resolve without treatment in a few weeks.
Acral bullae in a diabetic patient
Miscellaneous causes of blisters
Blisters can arise in the setting of atopic eczema, acute allergic contact dermatitis and plant dermatitis.
Vesicles on the hands and feet are seen in pompholyx which is also known as dyshidrotic eczema.
Certain photosensitive disorders also result in blistering and examples include polymorphic light eruption,
porphyria cutanea tarda and systemic lupus erythematosus.
Management of a patient presenting with blisters
A careful history with attention to the duration of disease, associated symptoms, medical
illnesses, drugs and family history
Examination to make note of the size and distribution of blisters, other skin rashes and
involvement of the mouth and eyes. The patient’s vital signs should also be taken into
consideration
Fluid from the blister may be sent for bacterial culture or viral analysis
Blood tests to look for inflammatory markers, renal and liver function, serum autoantibodies and
evidence of diabetes
Skin biopsy for the diagnosis of congenital or autoimmune blistering disorders with a sample for
direct immunofluorescence
Tense bullae should be drained using a sterile needle and their roofs should be left intact to act as
their own dressing
Hospital admission should be offered to those patients who require intravenous antibiotics or
have widespread skin lesions that need regular dressing
Topical antiseptics and cleansing moisturisers should be used to prevent infection
Involve the local dermatology team in the care of the patient
Use antiviral agents or appropriate antibiotics for primary and secondary infections
Systemic steroids may be needed for immunobullous disorders. Patients on long term steroids
require medication to prevent osteoporosis and gastric erosions and should be monitored for the
development of diabetes and hypertension